twoporedomain

Twoporedomain is a term used in molecular biology to describe potassium channels that contain two pore-forming domains within each subunit, a defining feature of the two-pore-domain potassium channel family (K2P). These channels typically assemble as dimers to form functional pores, providing conduction pathways for potassium ions that contribute to the cell’s resting membrane potential and baseline excitability. Each subunit houses two pore-forming loops (P1 and P2) and four transmembrane segments, and the dimeric assembly results in a channel with permeation pathways that support leak-like currents.

The K2P family includes several subfamilies, such as TWIK-related K+ channels (TWIK), TREK channels (including TREK-1 and TREK-2), TASK channels (TASK-1 to TASK-5), TALK channels (TWIK-related arachidonic acid-stimulated K+ channels), and TRESK (KCNK18). Members are broadly expressed in the nervous system and other tissues, where they help set membrane potential and modulate excitability. They differ in regulatory sensitivities and stimuli, being gated or modulated by extracellular pH, mechanical stretch, temperature, lipids, and intracellular signaling molecules. Pharmacological agents, including certain anesthetics, antidepressants, and opioids, can influence their activity.

Physiological and clinical relevance stems from their role in shaping neuronal firing, pain perception, mood regulation, and sleep patterns. Alterations in K2P channel function or expression have been linked to conditions such as chronic pain, epilepsy, migraines, and cardiac or metabolic disorders in various contexts. Ongoing research aims to clarify their gating mechanisms, physiological roles, and therapeutic potential as drug targets.

Etymology: the name reflects the presence of two pore-forming domains in each subunit, a hallmark distinguishing these channels from other potassium channel families.